Leptin is a hormonal product of adipocytes that has a role in the regulation of body weight and metabolism. In rodents, this fat-regulating substance acts as a metabolic signal to the reproductive axis and can reverse the inhibitory effects of food restriction on pubertal age and gonadotropin secretion. Numerous clinical studies in humans have reported correlations between leptin levels and metabolic (and weight) changes, but the role of leptin, if any, on the primate reproductive axis is unknown. Using a food restriction protocol that our colleague Dr. J. Cameron had shown to inhibit pulsatile luteinizing hormone (LH) in rhesus monkeys, we designed a study to determine if leptin could reverse this food-restricted LH inhibition. We fasted (water only) male monkeys (4-6 kg), Macaca mulatta, for 44 hours (h), during which time the animals received either leptin (134 g/kg BW/h, iv) or saline. Nightly patterns of LH were bioassayed using the mouse interstitial cell testosterone assay in blood samples that were collected every 20 minutes for two 12 h periods (before and 32-44 h after onset of the fast) and hourly for the first 18 h of the fast. In 4 of 4 monkeys treated with saline, there was complete suppression of LH pulses during fasting. Conversely, 3 of 4 leptin-treated monkeys showed distinct pulses of LH during the last 8 h of the fast. Moreover, mean LH levels during the same period were higher in the leptin-treated animals than in the vehicle-treated controls. Patterns of blood testosterone (T) in the individual males of the two groups showed similar trends to those of LH, although the 8-h mean levels of T between the leptin- and vehicle-groups were not different (P > 0.05). Our collaborators at the University of Washington are identifying possible neural targets for leptin's action by locating cells that contain leptin receptor mRNA. The results suggest that in primates, as in rodents, leptin is a metabolic signal to the reproductive axis and that neuropeptide Y and/or proopiomelanocortin containing cells may be mediators of leptin's action in the brain. Future efforts will focus on completion and publication of the findings, since the studies may provide a foundation for understanding relationships between eating disorders and certain reproductive problems.